KR20030039747A - Cosmetic Compositions Comprising Extract from Hop and Retinoid for Preventing Skin Aging - Google Patents

Abstract

PURPOSE: Provided is a cosmetic composition which contains as an active ingredient a hop extract and retinoid to improve the skin aging prevention effect. CONSTITUTION: A cosmetic composition for preventing the skin aging contains an extract of a hop (Humulus lupulus) and retinoid as an active ingredient. The hop extract is obtained by using a solvent such as water, alcohol having carbon numbers of 1-4 (such as methanol, ethanol, propanol and butanol), a mixture thereof, acetone, ethyl acetate, chloroform, and 1,3-butylene glycol. The retinoid is selected from the group consisting of retinol, retinal, retinyl acetate, retinyl propionate, retinyl linoleate, and retinyl palmitate. The composition contains 0.0001-10.0 wt.% of the hop extract and 0.001-5.0 wt.% of the retinoid.

Description

Cosmetic composition for preventing skin aging including hop extract and retinoids {Cosmetic Compositions Comprising Extract from Hop and Retinoid for Preventing Skin Aging}

The present invention relates to a cosmetic composition, and more particularly to a cosmetic composition for preventing skin aging comprising a hop extract and a retinoid as an active ingredient.

Among the skin aging phenomena are physiological aging and photo aging. In particular, photoaging is the biggest part of the aging of the skin. Photoaging is the aging of skin due to sunlight (ultraviolet rays), gradually changing the skin tissue, wrinkles, skin thickening, skin sagging, loss of skin elasticity , Skin roughness, skin dryness and skin stains are generated and these effects can be seen as a result of accumulation. Photoaging of the skin causes epidermis and dermal tissue to change, wrinkles develop, thicken the skin and elasticity gradually decreases.

Among the cosmetics for addressing skin aging are well known retinoids (Vitamin A) (see US Pat. No. 4603146; and US Pat. No. 4877805). Retinoids used in skin care cosmetics include Retinol: Vitamin A alcohol, Retinal: Vitamin A aldehyde, Retinyl acetate, Retinyl propionate , Retinyl linoleate and Retinyl palmitate. In particular, retinol, which is present in the human body, is essential for the differentiation and growth of epithelial tissues and has been widely used as a cosmetic because it has higher safety than other retinoids. However, these retinols are discolored and discolored when prescribed in the product despite their excellent anti-wrinkle and acne treatment effects, resulting in lowered potency and ineffective skin irritation even in small amounts. Has been extremely limited. In order to solve the above problems, the present inventors have developed a cosmetic composition which maintains a high functional effect for a long time by stabilizing a retinol, which is a conventional unstable high functional useful active substance, in threefold (see Korean Patent Application No. 2001-2001). 55103).

Currently, the ingredients developed as most cosmetics such as retinol have a weak clinical effect and improve the appearance of thick wrinkles very effectively, but have been found to hardly improve collagen bundle structure, skin elasticity and fine wrinkles. Efforts are being made to address this.

Throughout this specification, numerous patent documents are referenced and their citations are indicated. The disclosures of the cited patent documents are incorporated by reference herein in their entirety, and the level of the technical field to which the present invention belongs and the contents of the present invention are more clearly described.

The present inventors have diligently researched to develop a substance capable of greatly improving the skin anti-aging effect by using in combination with retinoids, especially retinol, which have been conventionally used in a cosmetic composition for preventing skin aging. As a result, when the hop extract is used in combination with a retinoid, skin aging The present invention has been completed by confirming that the prevention effect is remarkably improved.

Accordingly, it is an object of the present invention to provide a cosmetic composition for preventing skin aging.

The present invention provides a cosmetic composition for preventing skin aging comprising a hop extract and a retinoid as an active ingredient.

The inventors of the present invention, while improving the effectiveness of retinoids, in particular retinol, while at the same time to improve the problems of cosmetics containing retinol, when the hop extract is properly formulated with retinol to improve skin wrinkles, blemishes, It was confirmed that the synergistic effect was shown on the improvement of pigmentation such as freckles and blotch, skin elasticity enhancement and moisturizing effect.

The hop used as an active ingredient in the present invention is a vine stem plant whose name is wild as anywhere in Europe, Central Asia, North America, and Austria as Humulus lupulus. Female and male flowers bloom in different individuals, and many male flowers bloom at the end of the new shoot, and female flowers bloom between four bracts similar to lobule. The term "hof" in the conventional sense refers to dried, unripe female spikelets. On the other hand, the term "hop extract" in the present specification means that obtained by extracting from various organs (such as leaves, flowers, stems, fruits, etc.) of the hop, preferably means an extract obtained from immature female ear.

Hope is known to have excellent sedative and antimicrobial effects and to have effects on the genital, urinary and endocrine systems. In addition, hops as a cosmetic raw material have been used for the convergence effect and the stimulation alleviation effect.

Preferably, the hop extract in the present invention is (a) water, (b) anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), (c) the lower alcohol and water A mixed solvent, (d) acetone, (e) ethyl acetate, (f) chloroform or (g) 1,3-butylene glycol was obtained from the hops as an extraction solvent. Suitable amounts of the extraction solvent are 1-20 times the hop dry weight, more preferably 1-10 times.

On the other hand, it will be apparent to those skilled in the art that the extract of the present invention can be obtained a hop extract having substantially the same effect using not only the aforementioned extraction solvent but also other extraction solvents.

In addition, the extract of the present invention includes not only the extract by the above-mentioned extraction solvent, but also the extract that has undergone a conventional purification process. Obtained by various additional purification methods, such as, for example, separation using ultrafiltration membranes having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity). The fraction is also included in the hop extract of the present invention.

Hope extract of the present invention may be prepared in a powder state by an additional process such as vacuum distillation and freeze drying or spray drying.

Retinoid used as another active ingredient in the cosmetic composition of the present invention is a component commonly used in the art for wrinkle improvement, for example, retinol, retinal, retinyl acetate, retinyl propionate, retinyl lyne. Noliates and retinyl palmitates and the like, but is not limited thereto. Most preferably, the retinoid used in the present invention is retinol.

In a preferred embodiment of the present invention, the amount of hop extract is 0.0001 to 10.0% by weight, more preferably 0.005 to 5.0% by weight based on the total cosmetic composition. In a preferred embodiment of the present invention, the amount of retinoid is 0.001 to 5.0% by weight, more preferably 0.1 to 2.0% by weight based on the total cosmetic composition.

When the content of hop extract is less than 0.0001% by weight or the content of retinol is less than 0.001% by weight, no obvious anti-aging effect, in particular, wrinkle improvement cannot be expected, and the content of hop extract is greater than 10.0% by weight or retinol is 5.0. If the weight percentage is exceeded, there is no apparent increase in effect with increasing content.

Ingredients included in the cosmetic composition of the present invention include ingredients commonly used in cosmetic compositions in addition to hop extracts and retinol as active ingredients, and include, for example, conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavorings. And carriers.

The composition for alleviating the skin irritation of the present invention may be prepared in any formulation commonly prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactants -Can be formulated with, but not limited to, cleansing, oils, powder foundations, emulsion foundations, wax foundations, sprays, and the like. More specifically, it may be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.

When the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components. Can be.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide. Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

The cosmetic composition of the present invention has the use of skin anti-aging. As used herein, the term "anti-aging of skin" has the meaning encompassing comprehensively the prevention and treatment of skin aging. The cosmetic composition of the present invention prevents skin aging through skin wrinkle improvement, moisture retention, skin elasticity improvement, and the like, which is specified in the following examples. Therefore, anti-aging of the skin, which is the use of the present invention, is interpreted to include the use of wrinkle improvement, moisturizing improvement and skin elasticity improvement.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, it is to those skilled in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. Will be self-evident.

Preparation Example 1: Obtaining Hope Extract Using Various Extraction Solvents

Preparation Example 1-a

The hops were washed with purified water and dried to add 200 g of powdered hop powder to 2.5 L of 70% ethanol solution and heat extracted for 4 hours in a reflux extractor with a cooling condenser. Subsequently, the extract was filtered with a 300 mesh filter cloth, and the residue was extracted once more in the same manner. Then, the respective extracts were combined and filtered through Whatman No. 5 filter paper, and then the solvent was removed using a vacuum concentrator, and freeze-dried to obtain a dry weight of 31.4 g of hop extract.

Preparation Example 1-b

The hop was washed with purified water and dried, and then 200 g of powdered hop powder was added to 2.5 L of 70% methanol, and the same method as in Preparation Example 1-a was carried out to obtain a dry weight of 25.7 g of hop extract.

Preparation Example 1-c

The hops were washed with purified water and dried, and then 200 g of powdered hop powder was added to 2.5 L of purified water, and the same procedure as in Preparation Example 1-a was carried out to obtain a dry weight of 21.8 g of hop extract.

Preparation Example 1-d

The hops were washed with purified water, dried and 200 g of powdered hop powder was added to 2.5 L of acetone, and the same procedure as in Production Example 1-a was carried out to obtain a dry weight of 32.3 g of hop extract.

Preparation Example 1-e

The hop was washed with purified water and dried, and then 200 g of powdered hop powder was added to 2.5 L of normal butanol solution, and the same procedure as in Production Example 1-a was carried out to obtain a dry weight of 18.3 g of hop extract.

Preparation Example 1-f

The hops were washed with purified water, dried and 200 g of powdered hop powder was added to 2.5 l of ethyl acetate solution, and the same procedure as in Production Example 1-a was carried out to obtain a dry weight of 28.3 g of hop extract.

Preparation Example 1-g

The hops were washed with purified water and dried, and then 200 g of powdered hop powder was added to 2.5 l of 1,3-butylene glycol solution, and the same procedure as in Preparation Example 1-a was conducted to obtain 11.9 g of dry weight hop extract. Obtained.

Preparation Example 1-h

The hops were washed with purified water and dried, and then 200 g of powdered hop powder was added to 2.5 l of chloroform solution, and the same procedure as in Preparation Example 1-a was carried out to obtain a dry weight of 23.1 g of hop extract.

Examples and Comparative Examples

The raw materials of phases A and B in Table 1 were mixed uniformly and heated to 75 ° C., and then the two phases were emulsified. It was then cooled to 40 ° C., triple stabilized retinol (sphingosome) and hop extract and flavor and preservatives were added in turn and mixed to prepare the final cosmetic. Among the following components, sphingosomes are prepared according to the method developed by the present inventors (see Korean Patent Application No. 2001-55103), and hop extract is obtained in Preparation Example 1-a.

Unit (wt%) ingredient Example Comparative Example 1 Comparative Example 2 Sphingosome 10.0 10.0 - Hope Extract 2.0 - 2.0 A Cetostearyl alcohol 2.0 2.0 2.0 Glyceryl Stearate 1.5 1.5 1.5 Stearic acid 0.7 0.7 0.7 Squalane 5.0 5.0 5.0 Liquid paraffin 3.0 3.0 3.0 Trioctanoine 5.0 5.0 5.0 Ceramide 0.5 0.5 0.5 cholesterol 0.5 0.5 0.5 Cetearylglucoside 2.5 2.5 2.5 Cyclomethicone 3.0 3.0 3.0 Tocopheryl Acetate 0.2 0.2 0.2 BHT 0.05 0.05 0.05 B Purified water Remaining amount Remaining amount Remaining amount glycerin 4.0 4.0 4.0 1,3-butylene glycol 2.0 2.0 2.0 Xanthan Gum 0.1 0.1 0.1 EDTA-2Na 0.05 0.05 0.05 Incense, preservative Quantity Quantity Quantity system 100 100 100

Experimental Example 1: Skin Wrinkle Improvement Effect

Forty-five women aged 30 years or older (mean age 33.7 years old) were divided into three groups, with Examples in Group A, Comparative Example 1 in Group B, and Comparative Example 2 in Group C, respectively. It was applied during the week, and the objective evaluation of the expert and the subjective evaluation of the subject were performed. At this time, the evaluation criterion was extremely severely deteriorated to -3, and very improved to 3, and classified into a seventh grade to evaluate the improvement of skin wrinkles. The results of the objective evaluation are shown in Table 2 below, and the results of the subjective evaluation are shown in Table 3 below.

division Improvement of Skin Wrinkles (Objective Evaluation) Example Comparative Example 1 Comparative Example 2 first 12 weeks later first 12 weeks later first 12 weeks later Subject 1 0 3 0 2 0 One Subject 2 0 2 0 2 0 2 Subject 3 0 3 0 One 0 One Subject 4 0 3 0 2 0 2 Subject 5 0 3 0 One 0 One Subject 6 0 2 0 One 0 One Subject 7 0 3 0 3 0 2 Subject 8 0 2 0 2 0 One Subject 9 0 2 0 2 0 2 Subject 10 0 3 0 3 0 3 Subject 11 0 3 0 One 0 One Subject 12 0 3 0 2 0 2 Subject 13 0 3 0 2 0 2 Subject 14 0 3 0 3 0 2 Subject 15 0 2 0 One 0 One Average 0 2.67 0 1.87 0 1.60

division Skin wrinkle improvement (subjective evaluation) Example Comparative Example 1 Comparative Example 2 first 12 weeks later first 12 weeks later first 12 weeks later Subject 1 0 3 0 2 0 2 Subject 2 0 2 0 2 0 One Subject 3 0 3 0 One 0 One Subject 4 0 3 0 2 0 2 Subject 5 0 3 0 One 0 One Subject 6 0 3 0 2 0 2 Subject 7 0 3 0 3 0 2 Subject 8 0 2 0 2 0 One Subject 9 0 2 0 2 0 2 Subject 10 0 3 0 3 0 2 Subject 11 0 3 0 One 0 One Subject 12 0 3 0 2 0 2 Subject 13 0 3 0 2 0 One Subject 14 0 3 0 3 0 2 Subject 15 0 2 0 One 0 One Average 0 2.73 0 1.93 0 1.53

As can be seen from the above results, in the case of the Example, the objective evaluation and the subjective evaluation of the subject were 2.67 and 2.73, respectively, indicating that the wrinkle improvement effect was superior to 1.87 and 1.93 of Comparative Example 1 and 1.60 and 1.53 of Comparative Example 2, respectively. Can be. Thus, it can be seen that hop extract very effectively enhances the wrinkle improvement effect of retinol.

Experimental Example 2: Moisturizing Effect

In order to evaluate the moisturizing power of each cosmetic prepared in the above Examples and Comparative Examples, the moisture retention capacity and the water evaporation amount of the skin applied to each cosmetic was measured as follows:

Experimental Example 2-1: Measurement of Water Retention Capacity

In the constant temperature and humidity room of 22 ° C. and 45% RH, each of the cosmetics prepared in Examples and Comparative Examples was coated with a predetermined amount (0.03 g / 16 cm 2) in the lower half of 30 subjects, before application, and after 1 hour of application. The moisture content of the skin 2 hours after application was measured. At this time, a skin moisture content measuring instrument (corneometer CM820, koln-Germany) for measuring the electrical conductivity of the skin was used. The results are shown in Table 4 below.

division Example Comparative Example 1 Comparative Example 2 Skin electrical conductivity before application 50 50 50 Skin electrical conductivity 1 hour after application 93 78 73 Skin electrical conductivity 2 hours after application 82 67 65

Experimental Example 2-2: Measurement of Water Evaporation Amount

After applying the cosmetics to the test subjects in the same manner as in Example 2-1, the water evaporation amount of the skin was measured using a water evaporator (TEWA meter, koln-Germany) for 10 minutes at intervals of 2 minutes. The results are shown in Table 5 below.

division Example Comparative Example 1 Comparative Example 2 Water evaporation after 2 minutes 3% 6% 6% Water evaporation after 4 minutes 8% 14% 16% Water evaporation after 6 minutes 15% 23% 24% Water evaporation after 8 minutes 22% 29% 33% Water evaporation after 10 minutes 28% 35% 39%

As shown in the results of Experimental Examples 2-1 and 2-2, the cosmetics of the Examples exhibited higher electrical conductivity of the skin and less water evaporation than the cosmetics of Comparative Examples 1 or 2. Therefore, it can be seen that the cosmetic of the present invention exhibits an excellent moisturizing effect.

Experimental Example 3: Skin Elasticity Improvement Effect

In the constant temperature and humidity room of 22 ° C. and 45% RH, each cosmetic product prepared in Examples and Comparative Examples was placed in a constant amount (0.03 g / 16 cm 2) on the eyes of 30 healthy women (average age 33.7 years) for 12 weeks. Applied. In this case, the test subjects were divided into two groups, group A and group B, and the group A was applied to the left side of the eyes, and the cosmetic agent of Comparative Example 1 was applied to the right side of the eyes, and the group B of the example was placed on the left side of the eyes. The cosmetics of Comparative Example 2 were applied to the cosmetics and the right side of the eyes. Thereafter, skin elasticity of each group was measured using a skin elasticity measuring instrument (Cutometer SEM 575, C + K Electronic Co., Germany), and the results are shown in Table 6 below.

division Skin Elasticity Improvement (%) Example 45 Comparative Example 1 22 Comparative Example 2 23

As can be seen from the results of Table 6, it can be confirmed that the cosmetic composition of the Example containing the hop extract is much improved skin elasticity, compared to the cosmetic composition of Comparative Example 1 or 2. Therefore, it can be seen that the hop extract has an effective synergistic effect on the skin elasticity enhancing effect of retinol, which is presumed to be because the bundle structure of collagen is normally made by the hop extract and the elasticity of the skin is rapidly increased. .

Formulation Example 1

Formulation examples of the flexible lotion in the cosmetics containing hop extract and retinol are as follows. In all of the formulation examples below, the sphingosomes are triple stabilized retinol according to the method developed by the present inventors as in the above examples (see Korean Patent Application No. 2001-55103).

ingredient Content (% by weight) Sphingosome 0.2 Hope Extract 0.1 1,3-butylene glycol 6.0 glycerin 4.0 Oleyl alcohol 1.2 Stearic acid 1.0 Ceramide 0.5 cholesterol 0.5 Cetearylglucoside 2.5 ethanol 5.0 Propylparaben 0.1 Benzophenone-9 2.0 Carboxyl Vinyl Polymer 1.0 Pf. 962 0.2 Purified water Remaining amount system 100

Formulation Example 2

Formulation examples of the milk lotion in the cosmetics containing hop extract and retinol are as follows.

ingredient Content (% by weight) Sphingosome 2.0 Hope Extract 0.5 Propylene glycol 6.0 glycerin 4.0 Triethanolamine 1.2 Toco Ferring Acetate 3.0 Floating bluefin 5.0 Squalane 3.0 Macadamia Nut Oil 2.0 Stearic acid 1.0 Ceramide 0.5 cholesterol 0.5 Cetearylglucoside 2.5 Sorbitan sesquioleate 1.0 Propylparaben 0.1 Carboxyl Vinyl Polymer 1.0 Pf. Kn-921 0.3 Purified water Remaining amount system 100

Formulation Example 3

An example of the formulation of the nourishing cream in the cosmetic containing hop extract and retinol is as follows.

ingredient Content (% by weight) Sphingosome 10.0 Hope Extract 3.0 vaseline 7.0 glycerin 4.0 Triethanolamine 0.5 Tocopheryl Acetate 0.1 Liquid paraffin 10.0 Squalane 3.0 Beeswax 2.0 Stearic acid 1.0 Ceramide 0.5 cholesterol 0.5 Cetearylglucoside 2.5 Sorbitan sesquioleate 2.5 Propylparaben 0.05 Carboxyl Vinyl Polymer 1.0 Pf. Kn-942 0.2 Purified water Remaining amount system 100

Formulation Example 4

An example of the formulation of the massage cream in cosmetics containing hop extract and retinol is as follows.

ingredient Content (% by weight) Sphingosome 1.0 Hope Extract 0.3 Propylene glycol 6.0 glycerin 4.0 Triethanolamine 0.5 Tocopheryl Acetate 0.1 Liquid paraffin 30.0 Cetearyl Alcohol 2.0 Beeswax 2.0 Stearic acid 1.0 Ceramide 0.5 cholesterol 0.5 Cetearylglucoside 2.5 Sorbitan sesquioleate 2.5 Propylparaben 0.1 Carboxyl Vinyl Polymer 1.0 Pf. 951 0.2 Purified water Remaining amount system 100

Formulation Example 5

Formulation examples of packs in cosmetics containing hop extract and retinol are as follows.

ingredient Content (% by weight) Sphingosome 3.0 Hope Extract 0.5 Ethyl alcohol 3.0 EDTA-2Na 0.02 Propylene glycol 5.1 Glyceline 4.5 Cabopol 1.0 Stearic acid 1.0 Ceramide 0.5 cholesterol 0.5 Cetearylglucoside 2.5 Polyoxide 0.2 Pf. Kn-943 0.2 Purified water Remaining amount system 100

As described in detail above, the present invention provides a cosmetic composition for preventing skin aging. As the cosmetic composition of the present invention further comprises a hop extract in the conventional retinoid component, not only dramatically improves the wrinkle improvement effect of the conventional cosmetic composition using the retinoid as the sole active ingredient, but also improves the skin's moisturizing ability and skin elasticity. Also achieves the effect of, thereby preventing the aging of the skin.

Claims (7)

A skin composition for preventing skin aging comprising the hop extract and a retinoid as an active ingredient. The method of claim 1, wherein the hop extract is (a) water, (b) anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms, (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) A cosmetic composition for preventing skin aging, which is obtained by using ethyl acetate, (f) chloroform, or (g) 1,3-butylene glycol as an extraction solvent. The cosmetic composition for preventing skin aging according to claim 1, wherein the retinoid is selected from the group consisting of retinol, retinal, retinyl acetate, retinyl propionate, retinyl linoleate and retinyl palmitate. The cosmetic composition for preventing skin aging according to claim 3, wherein the retinoid is retinol. The cosmetic composition for preventing skin aging according to claim 1, wherein the amount of the hop extract is 0.0001 to 10.0 wt% based on the total cosmetic composition. The cosmetic composition for preventing skin aging according to claim 1, wherein the amount of retinoid is 0.001 to 5.0 wt% based on the total cosmetic composition. The method of claim 1, wherein the anti-wrinkle cosmetic composition is a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray Cosmetic composition for preventing skin aging, characterized in that it has a formulation selected from the group consisting of.